Our understanding of the biology of the innate immune systems is rapidly expanding. We are gaining an increasing understanding of the receptors expressed by NK cells that specifically mediate the inhibition and activation of these cells, as well as the ligands for these receptors. It is becoming clear that innate immune signals can dramatically modulate adaptive immune response. Emerging data are implicating NK cells and Other innate immune responses in the early control of HIV-1 replication during primary infection. The recent demonstration that it is possible to generate memory responses in the innate immune system raises the possibility that it may be feasible to use vaccines to enhance anti-viral innate immunity to help terminate or control very early HIV-1 infection. We will explore this possibility in the following aims: Aim 1. Recombinant canary-pox elicited innate responses and their contribution to shaping adaptive immune responses in rhesus monkeys Aim 2. Vaccination with KIR ligands for induction of immunologic memory for innate NK cell responses in rhesus monkeys and humans Aim 3. CD8+ T cell-produced factors and control of viremia The information gained in these studies about the anti-SIV and anti-HIV protective capacity of innate immune responses will lead directly to advances in vaccine design.